Induction of p21WAF/CIP1 during hyperoxia.
p21WAF/CIP1 is an important regulator of cell cycle progression (1-4). When induced, p21WAF/CIP1 protein inhibits cell cycle progression at the G1/S interface, resulting in growth arrest of the cell. To determine if p21WAF/CIP1 is involved in growth arrest and lung injury during hyperoxia, several cell lines were exposed to high levels of hyperoxia. p21WAF/CIP1 was found to be induced by 72 h in all three cell lines. Next, using an in vivo model, p21WAF/CIP1 was found to be induced at both the mRNA and protein level in neonatal murine lung born and maintained in hyperoxia. Localization of p21WAF/CIP1 was found in the peripheral airway cells. Hyperoxia-induced p21WAF/CIP1 expression was then shown to be mediated through the p53 pathway, using adult p53 mutant mice. These studies demonstrated that p21WAF/CIP1 is induced both in cells grown in culture and in neonatal and adult lung exposed to high levels of hyperoxia. Localization of p21WAF/CIP1 expression to the peripheral airway cells suggests that p21WAF/CIP1 may act to inhibit growth of alveoli in neonatal lung and delay repopulation of alveolar cells during hyperoxic administration.
McGrath
S A
SA
Department of Pediatrics, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.
D000818:Animals; D000831:Animals, Newborn; D002460:Cell Line; D002467:Cell Nucleus / Q000737:chemistry; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D004847:Epithelial Cells; D018507:Gene Expression Regulation, Developmental; D018496:Hyperoxia / Q000378:metabolism*; D008099:Liver / Q000166:cytology / Q000378:metabolism; D008168:Lung / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008817:Mice, Mutant Strains; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000502:physiology
C493957:Cdkn1a protein, mouse; C493958:Cdkn1a protein, rat; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53